Sodium Excretion of LCZ696 in Patients With Hypertension; Heart Failure and Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01353508
First received: March 16, 2011
Last updated: October 20, 2015
Last verified: October 2015
Results First Received: July 15, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Hypertension
Interventions: Drug: LCZ696
Drug: Valsartan

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
In each of the HF and HTN cohorts, 16 participants (total = 32) received LCZ696 or Valsartan in period 1. Then, there was a cross-over where participants received LCZ96 or Valsartan in period 2.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
LCZ696 to Valsartan - Heart Failure (HF) Cohort Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2.
Valsartan to LCZ696 - HF Cohort Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2.
LCZ696 to Valsartan - Hypertension (HTN) Cohort Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2.
Valsartan to LCZ696 - HTN Cohort Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2.

Participant Flow for 2 periods

Period 1:   Period 1 - First Intervention (7 Days)
    LCZ696 to Valsartan - Heart Failure (HF) Cohort     Valsartan to LCZ696 - HF Cohort     LCZ696 to Valsartan - Hypertension (HTN) Cohort     Valsartan to LCZ696 - HTN Cohort  
STARTED     8     8     8     8  
COMPLETED     8     8     8     7  
NOT COMPLETED     0     0     0     1  
Adverse Event                 0                 0                 0                 1  

Period 2:   Period 2 - Second Intervention (7 Days)
    LCZ696 to Valsartan - Heart Failure (HF) Cohort     Valsartan to LCZ696 - HF Cohort     LCZ696 to Valsartan - Hypertension (HTN) Cohort     Valsartan to LCZ696 - HTN Cohort  
STARTED     8     8     8     7  
COMPLETED     7     8     8     7  
NOT COMPLETED     1     0     0     0  
Withdrawal by Subject                 1                 0                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
LCZ696 to Valsartan - Heart Failure (HF) Cohort Participants in this arm received Valsartan 160 mg twice daily (bid) during open-label run-in, LCZ696 200 mg bid double blind treatment during period 1, Valsartan 160 mg bid during wash-out, and Valsartan 160 mg bid double blind treatment during period 2.
Valsartan to LCZ696 - HF Cohort Participants in this arm received Valsartan 160 mg twice daily bid during open-label run-in, Valsartan 160 mg bid during period 1, Valsartan 160 mg bid during wash-out, and LCZ696 200 mg bid double blind treatment during period 2.
LCZ696 to Valsartan - Hypertension (HTN) Cohort Participants in this arm received Valsartan 320 mg once daily (qd) during open-label run-in, LCZ696 400 mg qd double blind treatment during period 1, Valsartan 320 mg qd during wash-out, and Valsartan 320 mg qd double blind treatment during period 2.
Valsartan to LCZ696 - HTN Cohort Participants in this arm received Valsartan 320 mg qd during open-label run-in, Valsartan 320 mg qd during period 1, Valsartan 320 mg qd during wash-out, and LCZ696 400 qd bid double blind treatment during period 2.
Total Total of all reporting groups

Baseline Measures
    LCZ696 to Valsartan - Heart Failure (HF) Cohort     Valsartan to LCZ696 - HF Cohort     LCZ696 to Valsartan - Hypertension (HTN) Cohort     Valsartan to LCZ696 - HTN Cohort     Total  
Number of Participants  
[units: participants]
  8     8     8     8     32  
Age [1]
[units: Years]
Mean (Standard Deviation)
  63.3  (10.15)     67.6  (9.07)     58.0  (8.02)     61.6  (8.40)     62.6  (8.86)  
Gender  
[units: Participants]
         
Female     2     0     5     2     9  
Male     6     8     3     6     23  
[1] Age mean and standard deviation (SD) for HF cohort was 65.4 (9.57); age mean and SD for HTN cohort was 58.8 (8.15)



  Outcome Measures
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1.  Primary:   24-hour Urinary Sodium Excretion   [ Time Frame: day 1 ]

2.  Primary:   Cumulative 7-day Urinary Sodium Excretion   [ Time Frame: 7 day-cummulative (days 1 through 7) ]

3.  Secondary:   24-hour Diuresis   [ Time Frame: day 1 ]

4.  Secondary:   7-day Cumulative Diuresis   [ Time Frame: 7-day cumulative (days 1 through 7) ]

5.  Secondary:   Urinary Cyclic Guanosine Monophosphate (cGMP) Excretion Over 24 Hours   [ Time Frame: day 1, day 6, day 7 ]

6.  Secondary:   Percent Change From Baseline in Plasma Mid-regional Pro-atrial Natriuretic Peptide (MR-proANP) Biomarker   [ Time Frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 2, 4, 6 and 12 hours post dose on day 7 ]

7.  Secondary:   Percent Change From Baseline in Brain Natriuretic Peptide (BNP) Biomarker   [ Time Frame: 0.5, 1, 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 ]

8.  Secondary:   Percent Change From Baseline in Mid-regional Pro-adrenomedullin (MR-proADM) Biomarker   [ Time Frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 ]

9.  Secondary:   Percent Change From Baseline in C-type Natriuretic Peptide (proCNP) Biomarker   [ Time Frame: 2, 4, 6, 8 and 12 hours post dose on day 1; day 2; 0, 4, 6, 8 and 12 hours post dose on day 7 ]

10.  Secondary:   Percent Change From Baseline in C-terminal-proendothelin-1 (CT-proET-1) Biomarker   [ Time Frame: 12 hours post dose on day 1; 24 hours post dose on day 2; 0 and 12 hours post dose on day 7 ]

11.  Secondary:   Percent Change From Baseline in N-terminal-proBNP (NT-proBNP) Biomarker   [ Time Frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 ]

12.  Secondary:   Percent Change From Baseline in Aldosterone Biomarker   [ Time Frame: 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 6 and 12 hours post dose on day 7 ]

13.  Secondary:   Percent Change From Baseline in Urinary Electrolyte Excretion (Sodium, Potassium, Chloride and Calcium)   [ Time Frame: 2, 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 ]

14.  Secondary:   Percent Change From Baseline in Blood Plasma Creatinine   [ Time Frame: 4, 6 and 12 hours post dose on day 1; 24 hours post dose on day 2; 0, 4, 6 and 12 hours post dose on day 7 ]

15.  Secondary:   Glomerular Filtration Rate (GFR) Over Time   [ Time Frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 ]

16.  Secondary:   Renal Blood Flow (RBF) Over Time   [ Time Frame: 0, 2, 4 and 6 hours post dose on day 1; 0, 2, 4 and 6 hours post dose on day 7 ]

17.  Secondary:   Supine Systolic Blood Pressure   [ Time Frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 ]

18.  Secondary:   Supine Diastolic Blood Pressure   [ Time Frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 ]

19.  Secondary:   Supine Pulse Rate   [ Time Frame: 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 1; day 2; 0, 0.5, 1, 2, 4, 8 and 12 hours post dose on day 7 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Regarding LSM = 1218.56 for LCZ696 HTN cohort arm at Day 1, 1.0 hr post dose, the value was heavily inflated due to one participant with a very high change from baseline.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis
phone: 862-778-1873



Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01353508     History of Changes
Other Study ID Numbers: CLCZ696B2223
Study First Received: March 16, 2011
Results First Received: July 15, 2015
Last Updated: October 20, 2015
Health Authority: United States: Food and Drug Administration
Russia: Ministry of Health of the Russian Federation